Production of aldehydes by transition-metal catalyzed isomerization of unsaturated alcohols is well known. For example, allyl alcohol and methallyl alcohol isomerize to proprionaldehyde and isobutyraldehyde in the presence of metal complexes. (Davies, S. G. in Organotransition Metal Chemistry: Applications to Organic Synthesis, Pergamon, Oxford, 1982, 282-284.) However, the transformation often provides a complex reaction mixture having significant amounts of byproducts, thus complicating attempts to purify the desired aldehyde. Fortuitous selection of catalyst and solvent, on the other hand, can provide complete conversion to the desired aldehyde. One example involves the use of RuHCl(PPh3)3 to isomerize aliphatic allyl alcohols, which provides excellent conversion of secondary alcohols to ketones. The catalyst fails, however, to produce aldehydes from primary alcohols; no reaction occurs. (Sasson et al., Tetrahedron Lett., 1974, 4133-4136.)
In another example, isobutenol is completely isomerized to isobutyraldehyde upon treatment with RhHCO(PPh3)3 in trifluoroethanol at 70° C. in three hours. The foregoing reaction is solvent and catalyst dependent, however, and conversion drops to less than 70% when a ruthenium or copper catalyst is used or when the expensive trifluoroethanol is not used. Further, a method to separate the homogenous catalyst from the reaction product is not reported. (Strohmeier et al., J. Organometallic Chem., 1975, 86, C17-C19.) Trost reports the use of Cp(Ph3P)2RuCl (Cp=cyclopentadienyl) for the isomerization of allyl alcohols to aldehydes or ketones although conversion ranges from 31-92% depending on the substrate; separation of the product from the catalyst is conducted by expensive silica gel chromatography. (Trost et al., Tetrahedron Lett., 1991, 32, 3039-3042.)
Prior methods also reveal separation problems even if a reaction produces the target aldehyde. Since most rhodium complexes and some ruthenium complexes are also excellent decarbonylation catalysts, separation of the aldehyde from the catalyst by distillation is almost impossible due to decomposition of the aldehyde to form the decarbonylated product. (March, J. Advanced Organic Chemistry, 3rd Ed., John Wiley & Sons, New York, 1985, 655-656 and references therein.) Additional side reactions can include aldol condensation of the aldehyde products.
A method used to separate an aldehyde synthesized by isomerizing an allyl alcohol by contacting it with a molten phosphineirhodium reaction medium involves passing a carrier gas through the reaction mixture. (See, U.S. Pat. No. 4,950,797.) The vaporized carbonyl compound is removed from the emergent gas mixture by cooling. However, this method is limited to low-boiling aliphatic aldehydes since the boiling point of the product must be less than the temperature of the molten reaction mixture (180° C. at 1 atmosphere).
As mentioned above, problems encountered during the isomerization of allylic alcohols (e.g., to propionaldehyde) include the incomplete reaction and formation of byproducts. This complex mixture can be especially troublesome in the case of aryl-substituted allylic alcohols in which case equilibrium is established between the aldehyde and the aryl-conjugated unsaturated alcohol. As a result, the isomerization of 4-aryl-buten-1-ols to the corresponding aldehydes has not been reported in the literature.
Aryl-substituted aldehydes can be prepared by Heck addition of iodo- or bromo-benzene to unsaturated alcohols in the presence of a palladium catalyst, base and, in some cases, a phosphine ligand. (Chalk et al., J. Org. Chem., 1976, 41, 1206-1208; Melpolder et al., J. Org. Chem., 1976, 41, 265-272.) However, these palladium-catalyzed additions result in the production of a mixture of linear and branched addition products. In the case of 4-penten-1-ol, addition of aryl iodide resulted in improved ratios of the 5- to 4-arylation products (83:17) but required the use of stoichiometric amounts of additives (Bu4NCl, LiOAc, LiCl, DMF) and increased reaction time of 4 days. (Larock et al., Tetrahedron Lett., 1989, 30, 6629-6632.) Due to the complexity of the reaction mixtures, this type of process has not found use in industrial applications.